This is a Phase 2 Center of Biomedical Research Excellence (COBRE) application to further develop the Vermont Center on Behavior and Health (VCBH) at the University of Vermont (UVM). This multidisciplinary research center focuses on investigating relationships between unhealthy behavior patterns (e.g., substance abuse, physical inactivity, unhealthy food choices, non-adherence with recommended medical regimens) and risk for chronic disease and premature death. The overarching scientific priorities are (a) increasing understanding of the mechanisms underpinning vulnerability to unhealthy behavior patterns and (b) developing more effective behavior-change interventions. Advances in each of these areas are essential to improving U.S. population health, reducing health disparities, and curtailing spiraling health care costs. VCBH has made considerable progress in Phase 1 towards establishing a productive center of research excellence in this important area of biomedical research. VCBH currently consists of 20 UVM faculty members, highly accomplished external, internal, and community advisors, and collaborators from other IDeA states and beyond. The current faculty is multidisciplinary, evenly distributed across academic ranks, and highly productive, having published 118 articles in peer-reviewed journals and obtained $59,135,320 in additional external grant support during the initial four years of Phase 1 funding. We propose to continue prioritizing the mentoring of promising early-career faculty in Phase 2. We provided nine early-career faculty members with funded research projects and career-development support during Phase 1, using a multi-element mentoring plan that we will continue evaluating and refining during the proposed funding period. We propose continuing an Administrative Core that promotes effective communication, fiscal planning and oversight, supports a vibrant intellectual infrastructure, and directs and supports efforts to obtain external grant support. We have established two additional VCBH cores that we propose to continue, a Behavioral Economics and Intervention Sciences (BEIS) Core and a Collaboration, Dissemination, and Education (CDE) Core. The BEIS assists investigators with a decision-making and neuroimaging component to examine processes underpinning vulnerability to unhealthy behavior patterns, development of behavior-change interventions, and economic modeling of intervention cost-effectiveness. The CDE supports local, national, and international research collaborations, dissemination of new knowledge through a monthly lecture series, annual national conferences, annual Special Issues of the peer-reviewed journal Preventive Medicine, other publications, and educational efforts including seminars and workshops in behavior and health that are offered on the UVM campus and streamed live to collaborators and interested others. We are confident that continuing to develop and grow VCBH following this overall management plan will succeed in establishing a multidisciplinary center of research excellence in behavior and health with sustainable local, national, and international impact.